Gene Discovery- Immunotherapy has been most successful when targeted to differentiation antigens expressed on hematopoietic tumors and melanomas in large part because the target antigens are not expressed on essential cells or organs. Other cancers in which this approach could be successful are prostate, breast and ovary. To identify target antigens in prostate and breast cancers we have developed a computer based method to search the EST data base for ESTs that are expressed in prostate or breast cancer and not in other essential organs or cells. We have validated this approach experimentally and used it to identify several genes/proteins expressed in prostate cancer and not in essential normal organs. These include TARP, PAGE4, and GDEP. TARP is a mitochondrial protein that is also expressed in breast cancer. PAGE4 is a cytoplasmic protein and GDEP is a nuclear protein. We have discovered two new members of the MRP family, one of which (MRP9) is highly expressed in breast cancers. We have also developed an experimental approach to finding new immunotherapy targets in breast cancer by cloning new genes from membrane bound polysomal RNA. One of these that we have named BASE has the properties of a secreted protein and is found expressed in many breast cancers but only normal salivary gland. Base will be evaluated as a possible blood test for breast cancer.